title: Interventions for cutaneous Bowen's disease.
abstract: BACKGROUND
  Bowen's disease is the clinical term for in situ squamous cell carcinoma of the skin. Cutaneous lesions present as largely asymptomatic, well-defined, scaly erythematous patches on sun-exposed skin. In general, people with Bowen's disease have an excellent prognosis because the disease is typically slow-growing and responds favourably to treatment. Lesions are persistent and can be progressive, with a small potential (estimated to be 3%) to develop into invasive squamous cell carcinoma. The relative effectiveness of the available treatments is not known for Bowen's disease, and this review attempts to address which is the most effective intervention, with the least side-effects, for cutaneous Bowen's disease.
  
  
  OBJECTIVE
  To assess the effects of therapeutic interventions for cutaneous Bowen's disease.
  
  
  METHODS
  We searched the following databases up to September 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, Issue 9), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), and LILACS (from 1982). We also searched online trials registers. We checked the bibliographies of included and excluded studies and reviews, for further references to relevant randomised controlled trials (RCTs).
  
  
  METHODS
  We included all randomised controlled trials assessing interventions used in Bowen's disease, preferably histologically proven.
  
  
  METHODS
  Two authors independently carried out study selection and assessment of methodological quality.
  
  
  RESULTS
  The primary outcome measures were complete clearance of lesions after the first treatment cycle and recurrence rate at 12 months. Our secondary outcomes included the number of lesions that cleared after each treatment cycle, the number of treatment cycles needed to achieve clearance, the recurrence rates at > 12 months, cosmetic outcome, quality of life assessment, and adverse outcomes as reported by both participant and clinician.We included 9 studies, with a total of 363 participants. One study demonstrated statistically significantly greater clearance of lesions of Bowen's disease with MAL-PDT (methyl aminolevulinate with photodynamic therapy) when compared with placebo-PDT (RR (risk ratio) 1.68, 95% CI (confidence interval) 1.12 to 2.52; n = 148) or cryotherapy (RR 1.17, 95% CI 1.01 to 1.37; n = 215), but there was no significant difference when MAL-PDT was compared to 5-FU (5-fluorouracil). One study demonstrated statistically significantly greater clearance of lesions with ALA-PDT (5-aminolevulinic acid with photodynamic therapy) versus 5-FU (RR 1.83, 95% CI 1.10 to 3.06; n = 66), but no statistically significant difference in recurrence rates at 12 months (RR 0.33, 95% CI 0.07 to 1.53).Cryotherapy showed no statistically significant difference in clearance rates (RR 0.99, 95% CI 0.78 to 1.26) or recurrences at 1 year (RR 1.48, 95% CI 0.53 to 4.17) when compared to 5-FU in 1 study of 127 participants.One study compared imiquimod to placebo and demonstrated statistically significantly greater clearance rates in the imiquimod group (9/15 lesions) compared to placebo (0/16) (Fisher's Exact P value < 0.001). The imiquimod group did not report any recurrences at 12 months, but at 18 months, 2/16 participants in the placebo group had developed early invasive squamous cell carcinoma.
  
  
  CONCLUSIONS
  Overall, there has been very little good-quality research on treatments for Bowen's disease. There is limited evidence from single studies to suggest MAL-PDT is an effective treatment. Although cosmetic outcomes appear favourable with PDT, five-year follow-up data are needed. Significantly more lesions cleared with MAL-PDT compared to cryotherapy. No significant difference in clearance was seen when MAL-PDT was compared with 5-FU, but one study found a significant difference in clearance in favour of ALA-PDT when compared to 5-FU. There was no significant difference in clearance when cryotherapy was compared to 5-FU.The lack of quality data for surgery and topical cream therapies has limited the scope of this review to one largely about PDT studies. The age group, number, and size of lesions and site(s) affected may all influence therapeutic choice; however, there was not enough evidence available to provide guidance on this. More studies are required in the immunosuppressed populations as different therapeutic options may be preferable. Specific recommendations cannot be made from the data in this review, so we cannot give firm conclusions about the comparative effectiveness of treatments.
authors.affiliation: School of Nursing, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham, UK. fiona.bath-hextall@nottingham.ac.uk.
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Bath-Hextall
authors.forename: Rubeta N
authors.initials: RN
authors.lastname: Matin
authors.forename: David
authors.initials: D
authors.lastname: Wilkinson
authors.forename: Jo
authors.initials: J
authors.lastname: Leonardi-Bee
mesh_terms: D000622:Aminolevulinic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D000634:Aminoquinolines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001913:Bowen's Disease / Q000628:therapy*; D017679:Cryotherapy; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D000077271:Imiquimod; D009364:Neoplasm Recurrence, Local; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; D000077271:Imiquimod; D005472:Fluorouracil